Camptothecin (CPT) is an alkaloid extracted from Chinese endemic plant—Camptotheca acuminata—in 1966 by Wall et. al for the first time. In the early activity screening in vitro, camptothecin shows strong anti-tumor activity and significant inhibition against a variety of solid tumors and leukemia. However, camptothecin has poor water-solubility and strong adverse side-effects, thus it is limited for its application in cancer treatment. 10-Methoxycamptothecin is a natural derivative of camptothecin which has better anti-tumor activity than camptothecin, but also more toxic. In 1985, Hsiang Y. H. et. al found that camptothecin exhibits cytotoxic activity by inhibiting Topoisomerase I, which causes the people's attention to camptothecin again. Many researchers have begun to focus on modification and improvement to the chemical structure of camptothecin, and committed to improve its absorption in human body and enhance its therapeutic effects. So far, two kinds of camptothecin derivatives—Topotecan and Irinotecan—have been approved by the U.S. Food & Drug Administration (FDA) listed for the treatment of recurrent ovarian cancer and rectal/colon cancer. Another variety of derivatives such as 9-Nitrocamptothecin, 9-aminocamptothecin, CKD-602, DX-9815f, GI-147211 are also in various stages of clinical trials. The closed α-hydroxylactone ring in camptothecin structure is the essential structure for maintaining the anti-tumor activity thereof, but the α-hydroxylactone ring is easily hydrolyzed and open-looped in the human body to form a carboxylate structure, and the open-looped structure is easily bound to human serum protein so as to loss the anti-tumor activity.
